Enzymatically and hydrolytically stable dental preventive and restorative systems

ABSTRACT

A composition of matter includes one or more functionalized vinylbenzyl components of the formula 
     
       
         
         
             
             
         
       
     
     wherein n is an integer equal to or greater than 1 covalently connected to one or more R functional components; the one or more R functional groups selected from a group including one or more hydroxyl methyl (—CHOH—) moieties and/or derivatives thereof, one or more ethoxy (—CH 2 —CH 2 —O—) moieties and/or derivatives thereof, and one or more benzene derivatives; and ether links that connect the functionalized vinylbenzyl components and the R functional components.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/660,466 filed Mar. 17, 2015, and entitled “ENZYMATICALLY ANDHYDROLYTICALLY STABLE RESINS RESIN MONOMERS, AND RESIN COMPOSITES FORUSE IN DENTAL PREVENTIVE AND RESTORATIVE APPLICATIONS,” which claims thebenefit of U.S. Provisional Application Ser. No. 61/953,956 filed Mar.17, 2014, and entitled “ENZYMATICALLY AND HYDROLYTICALLY STABLE RESINSRESIN MONOMERS, AND RESIN COMPOSITES FOR USE IN DENTAL PREVENTIVE ANDRESTORATIVE APPLICATIONS” The disclosures of these two applications arehereby incorporated by reference.

BACKGROUND

Some current dental restorative applications may include: 1) a bisphenolA glycidyl methacrylate/triethylene glycol dimethacrylate(Bis-GMA/TEG-DMA) (see FIG. 1), and/or a urethane dimethacrylate-basedpolymer to provide a resin network, 2) reinforcing filler particlestreated with coupling agents (containing hydrolyzable ester connectinggroups) to bind the resin to the particles, and 3) bonding agents (alsocontaining hydrolyzable ester connecting groups). These systems andtheir accompanying use instructions may not produce satisfactorydurability and esthetics over time. In addition to a short averageservice life, these systems are subject to leaching of unreactedmonomers and system degradation products.

SUMMARY

Disclosed are enzymatically and hydrolytically stable resins for dentalapplications, and methods for producing such resin monomers that canyield highly cross-linked, strong and durable polymers. The resins andresin monomers for use in restorative dentistry withstand thechallenging conditions of the oral environment; however, the resins andresin monomers may be useful in additional strategic applications.

In an embodiment, a dental composite restorative system includes asilane coupling agent; a reinforcing filler; a surface active monomer;and a polymeric phase resin network, comprising a reaction product of aresin monomer having one or more functionalized vinylbenzyl ethercomponents of the formula

covalently connected to one or more R functional components, wherein nis an integer equal to 1 or greater than 1, the one or more R functionalcomponents selected from a first group consisting of:

-   -   one or more hydroxyl methyl (—CHOH—) moieties and/or derivatives        thereof;        -   one or more ethoxy (—CH₂—CH₂—O—) moieties and/or derivatives            thereof; and        -   one or more benzene derivatives, and    -   ether links that connect the functionalized vinylbenzyl        component(s) and the R functional component(s), and wherein X is        chosen from a second group consisting of a hydrogen and one or        more functional moieties, and the functional moieties consist of        one or more moieties chosen from a third group consisting of:        —CH₃, —C₂H₅, —OCH₃, —CF₃, —F, —Cl, —Br, —CN, —C₂H₅, —C₃H₇,        —C₄H₉, —OC₂H₅, —OCH₃H₇, and —OC₄H₉.

In an embodiment, a composition of matter includes one or morefunctionalized vinylbenzyl components of the formula

covalently connected to one or more R functional components; the one ormore R functional groups selected from a group including one or morehydroxyl methyl (—CHOH—) moieties and/or derivatives thereof, one ormore ethoxy (—CH₂—CH₂—O—) moieties and/or derivatives thereof, and oneor more benzene derivatives; and ether links that connect thefunctionalized vinylbenzyl components and the R functional components.

Also disclosed is a composition of matter consisting of one monomer or amixture of monomers that include one or more functionalized vinylbenzylcomponents of the formula

covalently connected to one or more R functional components. The one ormore R functional groups are selected from a group including one or morehydroxyl methyl (—CHOH—) moieties and/or derivatives thereof, one ormore ethoxy (—CH₂—CH₂—O—) moieties and/or derivatives thereof, and oneor more benzene derivatives; and ether links that connect thefunctionalized vinylbenzyl components and the R functional components,or the functionalized vinylbenzyloxy(s) and the R components(s) arelinked through one or more moieties chosen from a group consisting ofalkyl (—CH₂—, —CH₂CH₂—, —C₃H₆—, —C(i-propyl)₂-, and —C₄H₈—); alkoxy(—OCH₂—, —CH₂CH₂O—, —OC₃H₆—, and —OC₄H₈—); —C(CN)₂—; hydroxylsubstituted alkyl (—CHOH)—); and halide substituted alkyl (—C(CCl₃)₂—,—C(CBr₃)₂—, and —C(CF₃)₂—).

Further disclosed are compositions of matter as above made bypolymerizing the resin monomers using methods including free-radicalpolymerization, cationic polymerization, or anionic polymerization.

In various embodiments, the compositions of matter may be dentalmaterials that are used as restorative materials, laminate veneers,denture repairing materials, and sealants.

In other embodiments, the compositions of matter are dental materialsthat are used as dental adhesives, resin reinforced cements, and resinbonding or ceramic restorations.

DESCRIPTION OF THE DRAWINGS

The detailed description refers to the following figures in which likesymbols refer to like items, and in which:

FIG. 1 illustrates bisphenol A glycidyl methacrylate/triethylene glycoldimethacrylate (Bis-GMA/TEG-DMA) compounds;

FIG. 2 illustrates an example application as a dental compositerestorative system in which hydrolyzable methacrylate based-componentsare replaced with BPA-free and hydrolytically stable vinylbenzyl etherbased components;

FIGS. 3A-3G illustrate chemical structures/formulas of resin monomers;

FIGS. 4A-4F outline example synthesis plans for the resin monomers shownin FIGS. 3B-3G;

FIG. 5 illustrates and experimental process for evaluating the enzymaticdegradation performance of the herein disclosed resin monomers:

FIG. 6 illustrates degradation products produced by the interaction ofcurrent resin monomers and esterase enzymes;

FIG. 7 illustrates the resistance of the TEG-DVBE monomer to esterasedegradation;

FIGS. 8A and 8B illustrate, respectively, degradation profiles forBis-GMA and TEG-DMA monomers at different incubation time withesterases;

FIGS. 9A and 9B illustrate, respectively, the degradation ofBis-GMA/TEG-DMA polymers and the degradation resistance of TEG-DVBEpolymers in the presence of the esterase enzyme; and

FIGS. 10A and 10B are HPLC profiles illustrating degradation ofBis-GMA/TEG-DMA polymers and the degradation resistance of TEG-DVBEpolymers.

DETAILED DESCRIPTION

FIG. 1 illustrates current bisphenol A glycidyl methacrylate/triethyleneglycol dimethacrylate (Bis-GMA/TEG-DMA) compounds that are used in avariety of applications. One such application is as a component of adental composite restorative system for cavities. This current dentalcomposite restorative system further includes: 1) reinforcing fillerparticles treated with coupling agents (containing hydrolyzable esterconnecting groups) to bind the resin to the particles, and 2)dentin/enamel bonding agents (also containing hydrolyzable esterconnecting groups). However, current dental composite restorativesystems made of methacrylate-based resin have too short a service lifewith less than satisfactory durability and esthetics over time. Theshort service life of these systems coupled with leaching of unreactedmonomers, bisphenol A (BPA), and degradation products from these systemsmay require frequent dental rework and may raise other health issues.Although improvements have been made in the composite polymer and fillerproperties (see U.S. Pat. No. 7,241,856), the polymer chemistry(methacrylate-based resins) is fundamentally unchanged since itsintroduction in the early 1960s (see U.S. Pat. Nos. 3,066,112;3,179,623; and 3,194,784).

To overcome problems inherent in current dental composite restorativesystems, disclosed herein are resin monomers, resins, and resincomposites comprising polymers that are BPA-free, that experience lowshrinkage, and that are not susceptible to enzymatic and hydrolyticdegradation. Also disclosed are methods for producing the resinmonomers.

In an embodiment, the herein disclosed resins replace hydrolyzablemethacrylate-based resins with BPA-free and hydrolytically stablevinylbenzyl ether based resins. As an example, three co-polymerizablecompounds, Erythritol divinylbenzyl ether (E-DVBE), Triethyleneglycoldivinylbenzyl ether (TEG-DVBE) and Glycine,N-2-hydroxy-3-(4-vinylbenzyloxy) (NTG-VBE) (see FIG. 2 for examples oftheir structures) were synthesized, purified, and evaluated assubstitutes for currently used Bis-GMA, TEG-DMA, and NTG-GMA (Glycine,N-2-hydroxy-3-(2-methyl-1-oxo-2-propenyl)-oxypropyl-N-(4-methylphenyl),monosodium salt) [CAS No, 133736-31-9], respectively. Dental compositerestorative systems prepared with the herein disclosed resins, resincomposites, and accompanying adhesives will have better durabilitycompared with currently available Bis-GMA/TEG-DMA-based systems.

FIG. 2 illustrates an example application of a dental compositerestorative system that uses the herein disclosed example resins andresin monomers. Dental composite restorative system 10 includes areinforcing filler, a silane coupling agent, a polymeric phase resinnetwork, and a surface active monomer placed on so a tooth material. Theexample materials illustrated in FIG. 2:

1) Include easy handling resin monomers. The E-DVBE and TEG-DVBE havetwo terminal double bonds, which can each readily copolymerize, and canbe used in the polymeric phase resin network. The TEG-DVBE is used toadjust and control the viscosity of the monomers to obtain good handlingproperties of dental composite restorative systems. The NTG-VBE,incorporated in the form of the sodium, magnesium, or other salt, is theactive ingredient in dentin/enamel bonding agents, and can be used as asurface active monomer.

2) Eliminate all BPA moieties. Many professional publications report thedangers of BPA leaching from dental composites and sealants; thesedangers could decrease patients' willingness to obtain necessary dentalcare.

3) Eliminate potentially hydrolysable ester groups (contained inBis-GMA, TEG-DMA, and NTG-GMA—see FIG. 1) in either the cross-linkingmonomers of the composite or in its accompanying adhesive-bondingformulation. The herein disclosed materials have ether groups that arenot susceptible to salivary or other esterases, and thereby are moreresistant to degradation in the oral cavity.

4) Improve physical and chemical properties that can be achieved withcurrent resins. For example, E-DVBE is an amphiphilic compound with twohydrophobic vinylbenzyl groups at its ends and a flexible hydrophiliccenter (two hydroxyl groups from meso-erythritol). The vicinal hydroxylgroups can more easily form clusters of hydrogen bonds with the readilyaccessible hydroxyl groups of other such monomers. Modeling suggeststhat such clustering increases monomer density relative to its polymer,which should contribute to reduced polymerization shrinkage.

FIGS. 3A-3G illustrate chemical structures/formulas of the example resinmonomers disclosed herein. FIGS. 3A-3G also show how different theherein disclosed resin systems are from Bis-GMA/TEG-DMA-based resinsystems. Systems based on Bis-GMA/TEG-DMA contain undesirable estergroups [—C(═O)O—C—]. Many of these linking ester groups can eventuallycome apart by acidic, basic, or enzymatic-induced hydrolysis orsaponification in a stressful intraoral environment, especially at ornear polymer-tooth interfaces. Human saliva contains esterase that canhydrolyze ester-containing compounds. When subjected to thermal,mechanical and biochemical challenges, contemporary composite dentalrestorations can lose interfacial-sealing integrity leading to stainingand secondary decay. The herein disclosed resin systems replace all theester groups and use only hydrolytically and enzymatically-stable ethergroups.

The example resin monomers illustrated in FIGS. 3A-3G were synthesizedto enable simultaneous, side-by-side, comparative testing of allrestorative systems under the same environments and conditions.

FIG. 3A illustrates a general chemical structure/formula for the hereindisclosed resin monomers. As can be seen, the resin monomers may includea vinylbenzyl ether group. The attached R and X groups are defined withrespect to FIGS. 3B-3G. For example, for a resin monomer with onevinylbenzyl ether group, X₁ may be —H, —CH₃, or —C₂H₅, and —H ispreferred.

FIG. 3B illustrates the chemical structure/formula of resin monomerswhere one vinylbenzyl ether group (n=1) is attached to multi-hydroxylmethyl group(s). These monomers are amphiphilic compounds, and they alsomay have diluting functions as hydroxyethyl methacrylate (HEMA). For theresin monomer of FIG. 3B: m1=2, 3, or 4; X₁ may be —H, —CH₃, or —C₂H₅;X₂, X₃, X₆; and/or X₇ may be —H, —CH₃, —OCH₃, —CF₃, —F, —Cl, —Br, —CN,—C₂H₅, —C₃H₇, —C₄H₉, —OC₂H₅, —OC₃H₇, or —OC₄H₉; X₄ and/or X₅ may be —H,—CH₃, —OCH₃, —CF₃, —F, —Cl, —Br, —CN, —C₂H₅, —C₃H₇, —C₄H₉, —OC₂H₅,—OC₃H₇, or —OC₄H₉. The compound is erythritol vinylbenzyl ether (E-VBE)when all the X groups are —H and m₁=2. The synthesis plan for E-VBE isshown in FIG. 4A.

FIG. 3C illustrates the chemical structure/formula of resin monomerswhere also one vinylbenzyl ether group (n=1) is attached to a derivativeof glycine. These compounds may be an acid or the corresponding saltthereof, including sodium, magnesium, calcium, and strontium. For theresin monomers of FIG. 3C, X₁ may be —H, —CH₃, or —C₂H₅; X₂, X₃, X₆;and/or X₇ may be —CH₃, —OCH₃, —CF₃, —F, —Cl, —Br, —CN, —C₂H₅, —C₃H₇,—C₄H₉, —OC₂H₅, —OC₃H₇, or —OC₄H₉; X₄ and or X₅ may be —H, —CH₃, —OCH₃,—CF₃, —F, —Cl, —Br, —CN, —C₂H₅, —C₃H₇, —C₄H₉, —OC₂H₅, —OC₃H₇, or —OC₄H₉;X₈ and/or X₉ may be —H, —OH, —CH₃, —OCH₃, —CF₃, —F, —Cl, —Br, —CN,—C₂H₅, —C₃H₇, or —OC₂H₅; X₁₀ and/or X₁₁ may be —H, —CH₃, —OCH₃, —CF₃,—F, —Cl, —Br, —CN, —C₂H₅, or —OC₂H₅; X₁₂, X₁₃, and/or X₁₄ may be —H,—CH₃, —OCH₃, —CF₃, —F, —Cl, —Br, —CN, —C₂H₅, —C₃H₇, —C₄H₉, —OC₂H₅,—OC₃H₇, or —OC₄H₉; Y═H, Na, Ca, Mg, or Sr; and R₁=nothing (i.e., nofunctional groups), —(CH₂)_(m2) ⁻, or (CH₂CH₂O)_(m3) ⁻; m2 m3=1, 2, 3,4, or 5. More specifically, for X₁₀ and X₁₁, —H is preferred; for X₁₄,—CH₃, is preferred; for X₁₂ and X₁₃, —H is preferred; and for X₁₂ andX₁₃, ═—CH₃ and X₁₄═—H is highly preferred. These resin monomers aresurfactants; they may replace the surfactants (e.g., NTG-GMA), incurrent dental restorative composite systems; e.g., as a surface activemonomer in the adhesive-bonding components for dental resin composites.Compound NTG-VBE is an example when X₁ to X₁₃ are —H, X₁₄ is —CH₃, andR₁ is nothing. The synthesis plan for NTG-VBE is shown in FIG. 4B.

FIG. 3D illustrates the chemical structure/formula of resin monomerswhere two vinylbenzyl ether groups (n=2) are attached to ethoxygroup(s). For the resin monomer of FIG. 3D, m4=1, 2, 3, or 4; X, may be—H, —CH₃, or —C₂H₅; X₂, X₃, X₆; and/or X₇ may be —CH₃, —OCH₃, —CF₃, —F,—Cl, —Br, —CN, —C₂H₅, —C₃H₇, —C₄H₉, —OC₂H₅, —OC₃H₇, or —OC₄H₉; and X₄and/or X₅ may be —H, —CH₃, —OCH₃, —CF₃, —F, —Cl, —Br, —CN, —C₂H₅, —C₃H₇,—C₄H₉, —OC₂H₅, —OC₃H₇, or —OC₄H₉. The compound is triethyleneglycoldivinylbenzyl ether (TEG-DVBE) when all the X groups are —H and m₄=2.The synthesis plan for TEG-DVBE is shown in FIG. 4C.

FIG. 3E illustrates the chemical structure/formula of resin monomerswhere two vinylbenzyl ether groups (n=2) are attached to hydroxyl methylgroup(s). For the resin monomer of FIG. 3E, m₅=1, 2, 3, or 4; X₁ may be—H, —CH₃, or —C₂H₅; X₂, X₃, X₆; and/or X₇ may be —CH₃, —OCH₃, —CF₃, —F,—Cl, —Br, —CN, —C₂H₅, —C₃H₇, —C₄H₉, —OC₂H₅, —OC₃H₇, or —OC₄H₉; and X₄and/or X₅ may be —H, —CH₃, —OCH₃, —CF₃, —F, —Cl, —Br, —CN, —C₂H₅, —C₃H₇,—C₄H₉, —OC₂H₅, —OC₃H₇, or —OC₄H₉. The compound is erythritoldivinylbenzyl ether (E-DVBE) when all the X groups are —H and m₅=2. Thesynthesis plan for E-DVBE is shown in FIG. 4D.

The resin monomers with two vinylbenzyl groups ether (n=2) replace theBis-GMA/TEG-MA based dimethacrylate resins. As an example,triethyleneglycol divinylbenzyl ether (TEG-DVBE) and erythritoldivinylbenzyl ether (E-DVBE) were synthesized and purified to replacethe currently-used Bis-GMA and TEG-DMA.

FIG. 3F illustrates the chemical structure/formula of resin monomerswhere two vinylbenzyl ether groups (n=2) are attached to functionalgroups containing a benzyl ring. These monomers have a rigid core andthus may further improve the mechanical performance of the resins. Byadjusting the functional groups on X₉ to X₁₂ (for example, using —CF₃instead of —CH₃ groups), and the chain length of R₂ and R₃, thehydrophilicity/hydrophobicity of the resin monomers may be modified toimprove miscibility with other resin monomers and reduce waterabsorption in oral environments. For the resin monomer of FIG. 3F, X₁may be —H, —CH₃, or —C₂H₅; X₂, X₃, X₆; and/or X₇ may be —CH₃, —OCH,—CF₃, —F, —Cl, —Br, —CN, —C₂H₅, —C₃H₇, —C₄H₉, —OC₂H₅, —OC₃H₇, or —OC₄H₉;X₄ and/or X₅ may be —H, —CH₃, —OCH₃, —CF₃, —F, —Cl, —Br, —CN, —C₂H₅,—C₃H₇, —C₄H₉, —OC₂H₅, —OC₃H₇, or —OC₄H₉; X₉, X₁₀, X₁₁, and/or X₁₂ may be—H, —CH₃, —OCH₃, —CF₃, —F, —Cl, —Br, —CN, —C₂H₅, —C₃H₇, —C₄H₉, —OC₂H,—OC₃H₇, or —OC₄H₉. R₂, and/or R₃ may be nothing, —(CH₂)_(m6) ⁻, or—(CH₂CH₂H₂O)_(m7) ⁻; me may be 1, 2, 3, . . . or 18; and m7 may be 1, 2,3, 4, or 5. The compound is1,4-bis(1,1,1,3,3,3-hexafluoro-2-((4-vinylbenzyl)oxy)propan-2-yl)benzene(HF-DVBE) when X₉, X₁₀, X₁₁ and X₁₂ are —CF₃; R₂ and R₃ are nothing; andall of the other X groups are —H. The synthesis plan for HF-DVBE isshown in FIG. 4E.

FIG. 3G illustrates the chemical structure/formula of resin monomerswhere three vinylbenzyl ether groups (n=3) are attached to R. Thesemonomers have three polymerizable double bonds in each molecule andcreate more crosslinks using one molecule and thus change the dimensionand composition of crosslinks in the resin networks. As a result,stronger, tougher and more durable resin materials may form. For theresin monomers of FIG. 3G, X₁ may be —H, —CH₃, or —C₂H₅; X₂, X₃, X₆;and/or X₇ may be —CH₃, —OCH₃, —CF₃, —F, —Cl, —Br, —CN, —C₂H₅, —C₃H₇,—C₄H₉, —OC₂H₅, —OC₃H₇, or —OC₄H₉, X₄ and/or X₅ may be —H, —CH₃, —OCH₃,—CF₃, —F, —Cl, —Br, —CN, —C₂H₅, —C₃H₇, —C₄H₉, —OC₂H₅, —OC₃H₇, or —OC₄H₉;X₈, X₉ and/or X₁₀ may be —H, —OH, —CH₃, —OCH₃, —CF₃, —F, —C, —Br, —CN,—C₂H₅, —C₃H₇, or —OC₂H₅; R₄, R₅, and/or R₆ may be nothing, —(CH₂)_(m8)⁻, or —(CH₂CH₂O)_(m9) ⁻; m₈ may be 1, 2, 3, . . . or 18; and m₉ may be1, 2, 3, 4, or 5. The compound is4,4′,4″-(((2-methylbenzene-1,3,5-triyl)tris(methylene))tris(oxy))tris(methylene))tris(vinylbenzene)(B-TVBE) when R₄, R₅, and R₆ are nothing; and all of the X groups are—H. The synthesis plan for B-TVBE is shown in FIG. 4F.

The subject matter of FIGS. 3A-3G define various compositions of matterthat may be used, for example, in dental applications. For example, acomposition may include one or more functionalized vinylbenzylcomponents of the formula shown in FIG. 3A covalently connected to oneor more R functional components. The one or more R functional may begroups selected from a group consisting of one or more hydroxyl methyl(—CHOH—) moieties and/or derivatives thereof one or more ethoxy(—CH₂—CH₂—O—) moieties and/or derivatives thereof, and one or morebenzene (C₆H₆) and/or derivatives thereof; and ether links that connectthe functionalized vinylbenzyl components and the R functionalcomponents.

For these compositions of matter, the functionalized vinylbenzyloxy(s)and the R components(s) may be linked through one or more moietieschosen from a group consisting of alkyl (—CH₂—, —CH₂CH₂—, —C₃H₆—,—C(i-propyl)-, and —C₄H₈—); alkoxy (—OCH₂—, —CH₂CH₂O—, —OC₃H₆—, and—OC₄H₈—); —C(CN)₂—; hydroxyl substituted alkyl (—(CHOH)—); and halidesubstituted alkyl (—C(CCl₃)₂—, —C(CBr₃)₂—, and —C(CF₃)₂—).

In FIG. 3A-3G, in an embodiment, the symbol X may refer to a hydrogenatom. In some embodiments, one or more hydrogen atoms on the vinylbenzylcomponents may be replaced with functional moieties (to accelerate orslow down the rate of polymerization). The functional moieties may beone or more compounds or elements chosen from a group consisting of:—CH₃, —C₂H₅, —OCH₃, —CF₃, —F, —Cl, —Br, —CN, —C₂H₅, —C₃H₇, —C₄H₉,—OC₂H₅, —OC₃H₇, and —OC₄H₉.

In other embodiments, the R functional components may be one or multipleethoxy (—CH₂—CH₂—O—) moieties and their derivatives. In these otherembodiments, the ether links may be formed through reaction of halide(s)and alcohol(s) in the presence of a strong base, preferably sodiumhydride.

In still other embodiments, the R functional components contain hydroxylmethyl (—CHOH)— moieties, and the ether links are formed throughreactions of the functionalized vinylbenzyl halides and the primaryhydroxyl moieties of one of the compounds of the group consisting ofglycerol, erythritol, xylitol, mannitol, and sorbitol, in the presenceof a strong base, preferably sodium hydride, and wherein the secondaryhydroxyl group(s) are protected by protection groups while the etherlinks are formed, and the protection groups are removed after the etherlinks are formed.

In yet other embodiments, the R functional components contain hydroxylmethyl (—CHOH—) moieties and the ether links are formed throughreactions of the functionalized vinylbenzyl halides and hydroxylmoieties of one of the compounds of the group consisting of glycerol,erythritol, xylitol, mannitol, and sorbitol, in the presence of a strongbase, preferably sodium hydride, wherein the mole amount(s) offunctionalized vinylbenzyl halides is adjusted to be within a range ofthe mole amount of primary hydroxyls and the mole amount of primaryhydroxyls plus secondary hydroxyl moieties (—CHOH—).

In still other embodiments, the R functional components are selectedfrom the group consisting of N-(2-hydroxypropyl)-N-(p-styryl) glycine,N-(2-hydroxypropyl)-N-(phenyl) glycine,N-(2-hydroxypropyl)-N-(p-tolyl)glycine,N-(2-hydroxypropyl)-N-(3,5-dimethylphenyl)glycine, andN-(2-hydroxypropyl)-N-(vinylbenzyl)glycine, wherein each may be acidic,anionic, or preferably as a salt of one or more members of the groupconsisting of sodium, magnesium, calcium and strontium. In theseembodiments, an ether link connects each of the functionalizedvinylbenzyl groups with each of these R functional groups.

In some embodiments of the compositions of matter of FIGS. 3A-3G, theether link preferably is formed from a reaction of functionalizedvinylbenzyl glycidyl ether with members of the group consisting ofN(H)-(p-styryl)glycine, N(H)-(phenyl)glycine, N(H)-(p-tolyl)glycine,N(H)-(3,5-dimethylphenyl)glycine, and N(H)-(vinylbenzyl)glycine. Eachmay be anionic, or a salt of one or more members of the group consistingof sodium, magnesium, calcium and strontium. An ether link connects eachof the functionalized vinylbenzyl groups with each of these R functionalmoieties.

In still further embodiments, a composition of matter may consist of onemonomer or a mixture of monomers defined in FIGS. 3A-3G.

In the above-described compositions of matter, the resin monomer(s) maybe used with cyanoacrylate based, methacrylate based, or epoxy basedmonomers or polymers.

FIGS. 4A-4F outline synthesis plans for the example resin monomers ofFIGS. 3B-3G, respectively. For these plans, commercially availablematerials, purchased from Alfa Aesar, Sigma-Aldrich and TCI America,were used as received. Proton and carbon nuclear magnetic resonance (¹Hand ¹³C NMR) spectra were recorded on Bruker (600 MHz) and JOEL GSX (270MHz) spectrometers using 5 mm tubes. Chemical shifts were recorded inparts per million (ppm, δ) relative to tetramethylsilane (δ 0.00),dimethylsulfoxide-d5 (δ=2.50) or chloroform (δ=7.26). ¹H NMR splittingpatterns are designated as singlet (s), doublet (d), triplet (t),quartet (q), dd (doublet of doublets), m (multiplets), etc. Allfirst-order splitting patterns were assigned on the basis of theappearance of the multiplet. Splitting patterns that could not be easilyinterpreted are designated as multiplet (m) or broad (br). Fouriertransform infrared spectroscopy analysis (FTIR) was performed on aThermo Nicolet NEXUS 670 FTIR spectrometer. Analytical thin-layerchromatography (TLC) was carried out on EMD Millipore 60 F254 pre-coatedsilica gel plate (0.2 mm thickness). Visualization was performed usingUV irradiation (254 nm).

The detailed synthesis procedures are described with respect to thefollowing Examples 1-5:

Example 1 Synthesis of the Sodium Salt of NTG-VBE

The sodium salt of N (p-tolyl) glycine (0.05256 mol) was mixed with 100g of distilled water. The pH of the mixture was measured and adjusted toabout 9 by adding a IN aqueous NaOH solution drop-wise. The mixtureturned into a clear solution. To this stirred solution, a solutioncontaining vinylbenzyl glycidyl ether (0.05256 mol) and 0.0020 g of2,4,6-tri-tert-butylphenol (as a stabilizer to prevent prematurepolymerization) in 100 mL methanol was added drop-wise. A vacuum was notused in this synthesis because the 2,4,6-tri-tert-butylphenol requiresthe oxygen in air to be effective. Precipitation of the sodium salt ofNTG-VBE occurred on evaporation of methanol and some of the water. Thesodium salt of NTG-VBE was then collected by suction filtration andrecrystallized using acetone. The chemical structure was characterizedby ¹HNMR and ¹³CNMR. ¹H NMR (270 MHz, DMSO-d6) δ 7.67 (d, 2H), 7.23 (d,2H), 6.97 (d, 2H), 6.72 (d, 1H), 6.63 (d, 2H), 5.76 (d, 1H), 5.37 (s,1H), 5.25 (s, 1H), 4.63 (s, 2H), 4.29 (s, 2H), 3.38-3.75 (m, 5H), 2.32(s, 3H); ¹³C NMR (270 MHz, DMSO-d6) δ 147.6, 137.0, 138.7, 130.7, 129.9,129.6, 128.5, 114.3, 112.8, 75.5, 73.3, 66.5, 63.3, 62.1, 21.3

Example 2 Synthesis of 1,12-bis(4-vinylphenyl)-2,8,11-tetraoxadodecane

Triethylene glycol (8.02 mL, 9.01 g, 60 mmol) in DMF (30 mL) was addeddropwise to a stirred suspension of NaH (95%) (3.79 g, 150 mmol) in DMF(120 mL) at 0-4° C. under Ar₂ atmosphere over 30 minutes. After thereaction mixture was stirred for 2 hours at room temperature,4-Vinylbenzyl chloride (90%) (20.3 mL, 22.0 g, 120 mmol) in DMF (50 mL)was added dropwise over 30 minutes and the reaction mixture was stirredat room temperature for 18 hours. The reaction mixture was quenched byslow addition of a saturated NH₄Cl aqueous solution (50 mL) at roomtemperature. The resulting solution was diluted with distilled water(600 mL) and extracted with ethyl acetate (3×200 mL). The combined ethylacetate layers were washed with distilled water (2×200 mL). The organiclayer was dried over anhydrous magnesium sulfate, and the solvent wasremoved under reduce pressure to give crude product as a dark orangeoil. Flash column chromatography (silica, 30% ethyl acetate in hexane)afforded pure product as a pale yellow oil (27.5 g, 60%). The chemicalstructure was characterized by ¹HNMR and ¹³CNMR. ¹H NMR (600 MHz,DMSO-de) δ 7.43 (d, J=8.1 Hz, 4H), 7.29 (d, J=8.1 Hz, 4H), 6.72 (dd,J=17.8, 11.0 Hz, 2H), 5.81 (d, J=17.8, 2H), 5.24 (d, J=11.0 Hz, 2H),4.47 (s, 4H), 3.55 (m, 12H); ¹³C NMR (600 MHz, DMSO-d₆) δ 138.7, 136.9,136.7, 128.2, 126.5, 114.5, 72.2, 70.4, 70.3, 69.6.

Example 3 Synthesis of1,4-bis(1,1,1,3,3,3-hexafluoro-2-((4-vinylbenzyl)oxy)propan-2-yl)benzene

1,4-Bis(2-hydroxyhexafluoro-isopropyl)benzene (10 g, 24.4 mmol) wasadded to a stirred suspension of K₂CO₃ (10.1 g, 73.2 mmol) in DMF (70mL) under Ar₂ atmosphere. After reaction mixture was heated at 60° C.,4-Vinylbenzyl chloride (90%) (7.99 mL, 8.66 g, 51.2 mmol) in DMF (20 mL)was added dropwise over 30 minutes and the reaction mixture was stirredat 60° C. for 18 hours. The reaction mixture was cooled to roomtemperature and subsequently diluted with diethyl ether (500 mL) Theresulting mixture was washed with hydrochloric acid solution (1 M, 3×250mL), followed by washing with distilled water (2×250 mL). The organiclayer was dried over anhydrous magnesium sulfate, and the solvent wasremoved under reduce pressure to give crude product as a yellow solid.The crude product was recrystallized in Hexanes to afford pure productas a white solid (13.5 g, 86%). The chemical structure was characterizedby ¹HNMR and ¹³CNMR. ¹H NMR (270 MHz, DMSO-d6) δ 7.90 (s, 4H), 7.53 (d,J=8.2 Hz, 4H), 7.43 (d, J=8.2 Hz, 4H), 6.75 (dd, J=17.6, 10.9 Hz, 2H),5.87 (d, J=17.6, 2H), 5.28 (d, J=10.9 Hz, 2H), 4.64 (s, 4H); ¹³C NMR(270 MHz, DMSO-d6) δ 137.8, 136.5, 135.7, 130.1, 129.5, 128.7, 126.9,115.3, 68.2.

Example 4 Synthesis of (4R,5R)-2,2-dimethyl-4,5bis(((4-vinylbenzyl)oxy)methyl)-1,3-dioxolane

(−)-2,3-O-isopropylidene-D-threitol (5 g, 30.8 mmol) in DMF (20 mL) wasadded dropwise to a stirred suspension of NaH (95%) (1.95 g, 77.1 mmol)in DMF (60 mL) at 0-4° C. under Ar₂ atmosphere over 30 min. After thereaction mixture was stirred for 2 hours at room temperature,4-Vinylbenzyl chloride (90%) (9.60 mL, 10.4 g, 61.2 mmol) in DMF (50 mL)was added dropwise over 30 min and the reaction mixture was stirred atroom temperature for 18 hours. The reaction mixture was quenched by slowaddition of a saturated NH₄Cl aqueous solution (20 mL) at roomtemperature. The resulting solution was diluted with distilled water(300 mL) and extracted with ethyl acetate (3×100 mL). The combined ethylacetate layers were washed with distilled water (2×200 mL). The organiclayer was dried over anhydrous potassium carbonate, and the solvent wasremoved under reduce pressure to give crude product as a dark orangeoil.

Example 5 Synthesis of (2R,3R)-1,4-bis((4-vinylbenzyl)oxy)butane-2,3-diol

(4R,5R)-2,2-dimethyl-4,5-bis(((4-vinylbenzyl) oxy) methyl)-1,3-dioxolanecrude (Example 4) was added to a stirred suspension of Dowex® 50W2X (10g,) in MeOH (200 mL) at room temperature. The reaction mixture was thenstirred and refluxed at 70° C. for 18 hours. The mixture was filteredand the filtrate was evaporated under reduced pressure. The resultingmixture was diluted with distilled water and extracted with CH₂Cl₂(3×150 mL), and the combined organic layers were washed with distilledwater (3×200 mL). The organic layer was dried over anhydrous magnesiumsulfate, and the solvent was removed under reduced pressure to give acrude product as a yellow solid.

These resins may be employed in composites and the correspondingadhesives with specific functions as described above. In variousnon-limiting embodiments, different combinations of the resin monomersmay be incorporated into and polymerized to provide resin components ofa dental composite restorative system such as that illustrated in FIG.2. The resins have enzymatically and hydrolytically stable etherconnections (instead of hydrolyzable ester groups) that attach thepolymerizable vinylbenzyl groups of monomers of both the composite andits adhesive-bonding components.

An example instruction for the herein disclosed dental compositerestorative systems calls for an etching, washing, and removal of asmear layer on tooth surfaces to be treated. The smear layer representsa structurally weak layer that contains not only disrupted andfragmented tooth structures, but also extrinsic salivary pellicle,components of biofilms, and cariogenic microorganisms. It also plugsdentinal tubular openings, thereby preventing penetration of theadhesion-promoting monomeric components.

The vinylbenzyl ether groups readily homopolymerize and copolymerizewith methacrylate groups and other polymerizable groups including vinylgroups. The polymerization of the vinylbenzyl compounds may be initiatedusing initiators that are currently used in the methacrylate systems,for example: photo-initiators for wavelength 400-540 nm or dual-cureinitiators for both light and chemical initiation. An example ofphoto-initiator is the mixture of camphorquinone (CQ) and ethyl4-N,N-dimethylaminobenzoate (4E) at concentrations of 0.2 wt % and 0.8wt %, respectively, of the polymer matrix. The compounds also arepolymerizable using cationic and anionic polymerization mechanisms.

The herein disclosed resin composites may be used with or withoutfillers. The composite's reinforcing filler particles have shapes,sizes, and surface treatments that allow for a maximum filler/resinratio by surface treatment with different coupling agents attached bycovalent bonds, e.g., a combination of three types of silanes includingvinylbenzyltrimethoxy silane containing polymerizable vinyl groups toprovide covalent bonding and cross-linking with the monomeric phase,octyltrimethoxy silane for improved rheological properties andvinylbenzyldimethylammoniumpropyltrimethoxy silane chloride, to minimizeclustering or bridging and also contribute to interphase cross-linking.

The herein disclosed resins, resin monomers, and resin composites weresubjected to performance tests and evaluations as enumerated herein.

The Degree of Vinyl Conversion (DC):

The degree of vinyl conversion for the resins in sample disks afterphotopolymerization was determined using FTIR reflectancemicrospectroscopy (FTIR-RM). The Nicolet Continuum FT-IR microscope(Thermo Scientific, Madison, Wis.) operated in reflectance mode andinterfaced with a Nicolet 6700 FT-IR spectrophotometer was equipped withtwo liquid nitrogen-cooled mercury cadmium telluride detectors (MCT-A:11,700-650 cm⁻¹ and MCT-B: 11,700-400 cm⁻¹), a video camera, and acomputer-controlled x-y translation stage. Spectra were collected with64 scans from 650 cm⁻¹ to 4000 cm⁻¹ at 8 cm⁻¹ spectral resolution with abeam spot size of 90 μm×90 μm. Ten spectra each of three disks (8 mm indiameter and 1 mm in thickness) of every combination of resins wereobtained from the flat top and bottom of the disks. Each spot wasmanually focused before data collection. The reflectance spectra wereproportioned against a background of a gold coated slide and transformedto absorbance spectra using the Kramers-Kronig transform algorithm fordispersion correction, which converts the reflectance spectra toabsorbance-like spectra. The degree of vinyl conversion (DC) wascalculated as the reduction in the vinyl peak (1634 cm⁻¹) height usingthe phenyl absorbance peak (1610 cm⁻¹) as an internal standard. The peakheights were determined using the ISys software (Spectral Dimensions,Olney, Md., USA). The DC was the average of 30 spectra of three disks ofeach sample.

Enzymatic Degradation Test:

FIG. 5 illustrates an experimental process for evaluating the enzymaticdegradation performance of the herein disclosed resin monomers. Theevaluation process is based on the hypothesis that in an environmentcontaining esterases or cariogenic bacteria, traditional Bis-GMA andTEG-DMA monomers are converted to degradation products while the hereindisclosed TEG-DVBE does not degrade in the same environment. In FIG. 5,method 500 begins in block 505 by determining a suitable model foresterase activity. For example, cholesterol esterase (CE) activity maybe quantified by the degradation of a substrate and, as a result, thechange in the optical density (OD) formed by the degradation.Pseudocholinesterase activity may be tested by the degradation ofbutyrylthiocholin iodide (BTC) and by measuring changes in OD at awavelength of 405 nm. According to this observation, an enzyme activitymay be defined that is equivalent to the optical change per minute at405 nm, pH 7.0 and 25° C. This definition allows comparison betweenprevious degradations studies that used a similar definition of unitsand substrates.

Cholesterol ester activity may be tested by the degradation of fournitrophenyl-isomers; o-nitrophenylacetate (o-NPA), p-nitrophenylacetate(p-NPA), o-nitrophenylbutyrate (o-NPB) and p-nitrophenylbutyrate (p-NPB)by measuring changes in OD at a wavelength of 410 nm and defining the CEactivity as the change of absorbance of 0.01 OD per minute at 410 nm atpH 7.0 and 25° C.

In block 510, the esterase activity of model enzymes is measured and inblock 515, target molecules are determined for HPLC measurement.

Referring to FIG. 5, which illustrates degradation products produced bythe interaction of current resin monomers, specifically Bis-GMA andTEG-DMA, and esterase enzymes, methacrylic acid (MA) and2,2-Bis[4(2,3-hydroxypropoxy)phenyl]propane (bis-HPPP) are seen aspossible candidates (target molecules) for the HPLC analysis. Bis-HPPPis an organic compound structurally related to bisphenol A.

Returning to FIG. 5, the method 500 continues in block 520 with HPLCcalibrations. In block 525, the monomers and polymers are prepared andin block 530 the monomers and polymers are incubated with the modelenzymes. Finally, in block 540, the degradation of current and theherein disclosed resins are compared.

The inventors of the herein disclosed resin monomers (TEG-DVBE)performed the method 500 to compare degradation of TEG-DVBE andtraditional resin monomers (Bis-GMA and TEG-DMA) caused by the presenceof esterase enzymes. The degradation compounds were detected andquantified with HPLC. After a 24-hour incubation with the enzymes, nodegradation was found in new resin monomers. Both Bis-GMA and TEG-DMAwere decomposed dramatically by enzymes. Also evaluated was theresistance of new polymers made of TEG-DVBE and traditional polymersmade of a mixture of Bis-GMA and TEG-DMA in 1:1 mass ratio to esteraseenzymes. After a 16-day challenge with the enzymes, no degradation wasfound in new polymers. The traditional polymers showed significantdegradation by the enzymes. The test materials and methods are describedbelow. Enzyme preparation began with cholesterol esterase (CE) derivedfrom Pseudomonas bacteria (CE, C9281, Sigma, Saint Louis, Mo., USA) andPseudocholinesterase from horse serum (PCE, C4290, Sigma, Saint Louis,Mo., USA), which were reconstituted at desired concentrations inphosphate-buffered saline (D-PBS, 14190-144, Gibco®, Grant Island, N.Y.,USA) and sterile filtered using a 0.22 μm filter. The prepared enzymesolutions used for replenishing enzyme activity in the biodegradationexperiments were stored at −20° C. until needed.

Enzyme activity assay (i.e., CE activity) was determined bypara-nitrophenyl acetate (p-NPA) hydrolysis assay. P-NPA substrate(N8130, Sigma, Saint Louis, Mo., USA) was prepared by dissolving p-NPAin methanol (100 mM p-NPA), and diluting with a 100 mM sodium acetatebuffer, pH 5.0, to give a final p-NPA concentration of 1 mM. In atypical CE activity assay 50 μL p-NPA solution, 50 μL of CE solution (1unit/mL) and 100 μL sodium phosphate buffer (50 mM), pH 8.8, were addedto a 96-well plate to give a final pH of 7.0, and the change ofabsorbance over time was measured at 410 nm at 25° C. using a SpectraMaxMicroplate reader (Molecular Devices, Sunnyvale, Calif., USA). One unitof CE activity is defined as a change of absorbance of 0.01 per minute.CE enzyme inhibition was assessed with the addition of 4 μL ofphenylmethanesulfonylfluoride (PMSF, 50 mM in anhydrous ethanol). PCE (1unit/mL) activity was determined with acetylcholinesterase activityassay kit (MAKI 19, Sigma, Saint Louis, Mo., USA) by measuring a changein absorbance at 412 nm, using butylthiocholine (BTC) as a substrate.One unit of PCE activity was defined as the formation of 1.0 μmol ofbutyrate released per 1 mL of enzyme per minute at pH 7.5 and 25° C.

For polymer preparation, the composition of conventional resin was 50:50wt % Bis-GMA:TEG-DMA (Esstech, Essington, Pa., USA) with 0.2 wt %Camphorquinone (CQ, 124893, Aldrich, Saint Louis, Mo., USA) and 0.8 wt %ethyl 4-(dimethylamino)benzoate (DMAEMA, E24905, Aldrich, Saint Louis,Mo., USA as the photoinitiator system. TEG-DVBE was mixed with 1 wt %IIRGACURE 819 (I-819) and 1 wt % bis(4-tert-butylphenyl)iodoniumhexafluorophosphosphate (DPI) as a photoinitiation system.Photoinitiation systems for each composition were selected to achieveresins with high degree of conversion. Monomer samples were filled intoa 3 mm radius, 1 mm height cylindrical Teflon mold, and between twoMylar films at the top and the bottom to prevent oxygen-inhibition ofthe surface layer. Additionally, glass slides were used to flatten thesurface. The samples were photocured with a Triad 2000 visible lightcuring unit (Dentsply Trubyte, York, Pa., USA) for one minute on eachside. The hardened pellets with a 75 mm2 surface area were post-curedovernight in a vacuum oven at 60° C., then incubated in D-PBS at 37° C.with stirring for 24 hours to remove any unreacted monomers. Pelletswere then rinsed with distilled water and vacuum dried until they reacha constant mass.

For monomer degradation, Bis-GMA, TEG-DMA, and TEG-DVBE monomers wereeach dissolved in DMSO (20 mM monomer), and diluted in D-PBS to give amonomer concentration of 0.4 mM. Monomer solutions (750 μL) wereincubated with CE or PCE (750 μL, 2 units/mL) for 24 hours at 37° C.(n=3). PMSF at 1.0 mM and 0.5 mM were used as negative controls for CEand PCE, respectively. At 1, 8, and 24 hours of incubation, 400 μL ofmedia was removed from each sample and the enzyme activity was inhibitedwith the addition of 266 μL methanol. Samples were centrifuged at 16000rcf for 30 minutes to eliminate large particles and stored at 4° C.until analysis with HPLC.

For polymer degradation, cured polymer pellets were incubated with 500μL 1 unit/mL CE or PCE, with media volume to polymer resin surface arearatio of 6.6 ul per mm, for up to 16 days at 37° C. (n=3). PMSF at 1.0mM and 0.5 mM were used as negative controls for CE and PCE,respectively. The incubation media was replaced every 48 hours tomaintain nominal enzyme activity. Each pooled media was quenched withthe addition of 400 μL methanol. The media from 2, 8, and 16 days ofincubation periods were pooled for HPLC analysis. The pooled media werecentrifuged at 16000 rcf for 30 minutes and stored at 4° C. untilanalysis with HPLC. Samples were also centrifuged for 30 minutes toeliminate large particles and stored at 4° C. until analysis with HPLC.

For HPLC analysis, an Agilent 1290 Infinity Binary HPLC System was usedfor the chromatographic separation and quantification of the degradationproducts. Specifically, the disappearance of TEG-DMA, Bis-GMA andTEG-DVBE monomers, as well as the appearance of methacrylic acid (MA,155721, Aldrich, St. Louis, Mo., USA) derived from TEG-DMA and Bis-GMAand bishydroxy propoxy phenyl propane (bis-HPPP, 15137, Fluka, SaintLouis, Mo., USA) from Bis-GMA as degradation products where of interest.A Zorbex Extend 5 μm C18 0.10 4.6×250 mm column (770450-902, AgilentTechnology, Santa Clara, Calif., USA) was used for the separation ofproducts. The mobile phase consisted of 2 mM buffer solution ofHPLC-grade ammonium acetate (AX1222, EMD Chemicals Inc., Billerica,Mass., USA) with pH adjusted to 3.0 with 6.0 N hydrochloric acid(A144-500, Fisher Scientific, Fair Lawn, N.J., USA) and HPL-grademethanol (MX0475, EMD Chemicals Inc., Billerica, Mass., USA). Theseparation was achieved with 50% to 100% methanol in ammonium acetatebuffer gradient for 30 minutes to provide comparison with reported testsresults for current monomers. Degradation products were detected byabsorbance at 215 nm using a 1290 Infinity variable wavelength UVdetector. Calibration curves were created by linear correlation of peakarea to known concentrations of the analytes in methanol and the amountof product formed from both monomer and polymer degradation wereanalyzed.

FIG. 7 HPLC profiles illustrate the resistance of the TEG-DVBE monomerto esterase degradation. FIG. 7 is a chromatogram of the TEG-DVBEmonomer exposed to an environment of the enzymes CE and PCE and thesolvent D-PBS, and shows absorbance of these molecules versus time. Ascan be seen, no degradation products were found in any of theconditions.

FIGS. 8A and 8B illustrate, respectively, degradation profiles forBis-GMA and TEG-DMA monomers up to 24 hours. FIG. 8A illustrates thedegradation of the Bis-GMA monomer in the presence of the CE enzyme. Thefirst plot illustrates absorbance of MA. The second plot illustratesabsorbance of Bis-HPPP. The third plot illustrates absorbance ofBis-GMA.

FIG. 8B illustrates the degradation of TEG-DMA in the presence of thePCE enzyme up to 24 hours. The first plot illustrates absorbance of MAand the second plot illustrates the absorbance of TEG-DMA.

FIGS. 9A and 9B illustrate, respectively, the degradation of Bis-GDMAand TEG-DMA monomers and the degradation of TEG-DVBE monomers in thepresence of the esterase enzyme. Both figures plot incubation time (indays) versus cumulative absorption of MA in the presence of CE, PCE, andD-PBS. As can be seen, the Bis-GMA and TEG-DMA monomers show significantaccumulation of MA while (in FIG. 9B), TEGVBE shows negligibleaccumulation of MA.

FIGS. 10A and 101B are chromatograms illustrating degradation ofBis-GDMA and TEG-DMA monomers and the TEG-DVBE monomer.

The above description refers to resins, resin composites, and adhesivesfor use in a dental composite restorative system. However, thesematerials in various combinations may be used in other systems whereester-based degradation and BPA-free conditions are a concern. Forexample, the materials may be used in certain food-packing applications,and in prosthetic devices.

We claim:
 1. A dental composite restorative system, comprising: a silanecoupling agent; a reinforcing filler; a surface active monomer; and apolymeric phase resin network, comprising: a reaction product of a resinmonomer having one or more functionalized vinylbenzyl ether componentsof the formula

covalently connected to one or more R functional components, wherein nis an integer equal to 1 or greater than 1, the one or more R functionalcomponents selected from a first group consisting of: one or morehydroxyl methyl (—CHOH—) moieties and/or derivatives thereof; one ormore ethoxy (—CH₂—CH₂—O—) moieties and/or derivatives thereof; and oneor more benzene derivatives, and ether links that connect thefunctionalized vinylbenzyl ether component(s) and the R functionalcomponent(s), wherein X is chosen from a second group consisting of ahydrogen and one or more functional moieties, and the functionalmoieties consist of one or more elements chosen from a third groupconsisting of: —CH₃, —C₂H₅, —OCH₃, —CF₃, —F, —Cl, —Br, —CN, —C₂H₅,—C₃H₇, —C₄H₉, —OC₂H₅, —OC₃H₇, and —OC₄H₉.
 2. The dental compositerestorative system of claim 1, wherein the ether links are one or moremoieties chosen from a fourth group consisting of: alkyl (—CH₂—,—CH₂CH₂—, —C₃H₆—, —C(i-propyl)₂-, and —C₄H₈—); alkoxy (—OCH₂—,—CH₂CH₂O—, —OC₃H₆—, and —OC₄H₈—); —C(CN)₂—; hydroxyl substituted alkyl(—(CHOH)—); and halide substituted alkyl (—C(CCl₃)₂—, —C(CBr₃)₂—, and—C(CF₃)₂—).
 3. The dental composite restorative system of claim 1,wherein X is a hydrogen atom; and wherein one or more of the hydrogenatoms is replaced with functional moieties consisting of one or morecompounds or elements chosen from a fifth group consisting of —CH₃,—C₂H₅, —OCH₃, —CF₃, —F, —Cl, —Br, —CN, —C₂H₅, —C₃H₇, —C₄H₉, —OC₂H₅,—OC₃H₇, and —OC₄H₉.
 4. The dental composite restorative system of claim1, wherein the R functional component(s) are one or multiple ethoxy(—CH₂—CH₂—O—) moieties and their derivatives, and their ether links areformed through reaction of halide(s) and alcohol(s) in the presence of astrong base, preferably sodium hydride.
 5. The dental compositerestorative system of claim 1, wherein the R functional component(s)contain hydroxyl methyl (—CHOH)— moieties, and the ether links areformed through reactions of the functionalized vinylbenzyl halides andthe primary hydroxyl moieties of one of the compounds of a sixth groupconsisting of glycerol, erythritol, xylitol, mannitol, and sorbitol, inthe presence of a strong base, preferably sodium hydride, and whereinthe secondary hydroxyl group(s) are protected by protection groups whilethe ether links are formed, and the protection groups are removed afterthe ether links are formed.
 6. The dental composite restorative systemof claim 1, wherein the R functional component(s) contain hydroxylmethyl (—CHOH—) moieties and the ether links are formed throughreactions of the functionalized vinylbenzyl halides and hydroxylmoieties of one of the compounds of the sixth group consisting ofglycerol, erythritol, xylitol, mannitol, and sorbitol, in the presenceof a strong base, preferably sodium hydride, and wherein the moleamount(s) of functionalized vinylbenzyl halides is adjusted to be withina range of the mole amount of primary hydroxyls and the mole amount ofprimary hydroxyls plus secondary hydroxyl moieties (—CHOH—).
 7. Thedental composite restorative system of claim 1, wherein the R functionalcomponents are selected from a seventh group consisting of:N-(2-hydroxypropyl)-N-(p-styryl) glycine, N-(2-hydroxypropyl)-N-(phenyl)glycine, N-(2-hydroxypropyl)-N-(p-tolyl) glycine,N-(2-hydroxypropyl)-N-(3,5-dimethylphenyl) glycine, andN-(2-hydroxypropyl)-N-(vinylbenzyl) glycine, wherein each member of theseventh group may be acidic, anionic, or preferably a salt of one ormore members of an eighth group consisting of sodium, magnesium, calciumand strontium, and wherein an ether link connects each of thefunctionalized vinylbenzyl group(s) with each of the seventh group Rfunctional component(s).
 8. The dental composite restorative system ofclaim 7, wherein the ether link preferably is formed from a reaction offunctionalized vinylbenzyl glycidyl ether with members of a ninth groupconsisting of N(H)-(p-styryl) glycine, N(H)-(phenyl) glycine,N(H)-(p-tolyl) glycine, N(H)-(3,5-dimethylphenyl) glycine, andN(H)-(vinylbenzyl) glycine, wherein each member of the ninth group maybe anionic, or a salt of one or more members of the eighth groupconsisting of sodium, magnesium, calcium and strontium, and wherein anether link connects each of the functionalized vinylbenzyl component(s)with each of the members of the ninth group.
 9. The dental compositerestorative system of claim 1, used as dental materials for restorativematerials, fabrication of laminate veneers, denture repairing materials,dental adhesives, resin reinforced cements, resins for bonding ceramicrestorations, and sealants.
 10. A dental composite restorative system,comprising: a polymerized resin monomer comprising at least onefunctionalized vinylbenzyl ether component, wherein the functionalizedvinylbenzyl ether component comprises elements chosen from a first groupconsisting of a hydrogen and one or more functional moieties, andwherein the functional moieties consist of one or more elements chosenfrom a second group consisting of: —CH₃, —C₂H₅, —OCH₃, —CF₃, —F, —Cl,—Br, —CN, —C₂H₅, —C₃H₇, —C₄H₉, —OC₂H₅, —OC₃H₇, and —OC₄H₉; eachfunctionalized vinylbenzyl ether component covalently connected to afunctional component; and the functional component is selected from athird group consisting of: one or more hydroxyl methyl (—CHOH—) moietiesand/or derivatives thereof, one or more ethoxy (—CH₂—CH₂—O—) moietiesand/or derivatives thereof, and one or more benzene derivatives.
 11. Thedental composite restorative system of claim 10, comprising one or moreof: a silane coupling agent; a reinforcing filler; and a surface activemonomer.
 12. The dental composite restorative system of claim 11 used aslaminate veneers, denture repairing materials, dental adhesives, resinreinforce cements, placement of ceramic restorations, and sealants. 13.A dental composite restorative system, comprising: a polymerizedcomposition formed by polymerization of a monomer composition, themonomer composition, comprising: one or more functionalized vinylbenzylcomponents of the formula

wherein n is an integer equal to or greater than 1, and one or more Rfunctional components, and ether links connecting the one or morefunctionalized vinylbenzyl components and the one or more R functionalcomponents, wherein the one or more R functional components are selectedfrom a first group consisting of one or more hydroxyl methyl (—CHOH—)moieties and/or derivatives thereof, one or more ethoxy (—CH₂—CH₂—O—)moieties and/or derivatives thereof, and one or more benzenederivatives.
 14. The dental composite restorative system of claim 13,wherein the ether links comprise one or more moieties chosen from asecond group consisting of alkyl (—CH₂—, —CH₂CH₂—, —C₃H₆—,—C(i-propyl)₂-, and —C₄H₈—); alkoxy (—OCH₂—, —CH₂CH₂O—, —OC₃H₆—, and—OC₄H₈—); —C(CN)₂—; hydroxyl substituted alkyl (—(CHOH)—); and halidesubstituted alkyl (—C(CCl₃)₂—, —C(CBr₃)₂—, and —C(CF₃)₂—).
 15. Thedental composite restorative system of claim 13, wherein the Xcomponents are one of a hydrogen atom and one or more functionalmoieties to accelerate or slow down the rate of polymerization, thefunctional moieties being one or more compounds or elements chosen froma third group consisting of —CH₃, —C₂H₅, —OCH₃, —CF₃, —F, —Cl, —Br, —CN,—C₂H₅, —C₃H₇, —C₄H₉, —OC₂H₅, —OC₃H₇, and —OC₄H₉.
 16. The dentalcomposite restorative system of claim 13, wherein the R functionalcomponents further comprise one or multiple ethoxy (—CH₂—CH₂—O—)moieties and their derivatives, and wherein, the ether links are formedthrough reaction of halide(s) and alcohol(s) in the presence of a strongbase, preferably sodium hydride.
 17. The dental composite restorativesystem of claim 13, wherein the R functional components contain hydroxylmethyl (—CHOH—) moieties, and the ether links are formed throughreactions of functionalized vinylbenzyl halides and primary hydroxylmoieties of one of the compounds of a fourth group consisting ofglycerol, erythritol, xylitol, mannitol, and sorbitol, in the presenceof a strong base, preferably sodium hydride, and wherein the secondaryhydroxyl group(s) are protected by protection groups while the etherlinks are formed, and the protection groups are removed after the etherlinks are formed.
 18. The dental composite restorative system of claim13, wherein the R functional components contain hydroxyl methyl (—CHOH—)moieties and the ether links are formed through reactions offunctionalized vinylbenzyl halides and hydroxyl moieties of one of thecompounds of a fifth group consisting of glycerol, erythritol, xylitol,mannitol, and sorbitol, in the presence of a strong base, preferablysodium hydride, wherein the mole amount(s) of functionalized vinylbenzylhalides is adjusted to be within a range of the mole amount of primaryhydroxyls and the mole amount of primary hydroaxyls plus secondaryhydroxyl methyl (—CHOH—) moieties.
 19. The dental composite restorativesystem of claim 13, wherein the R functional components are selectedfrom a sixth group consisting of:N-(2-hydroxypropyl)-N-(p-styryl)glycine,N-(2-hydroxypropyl)-N-(phenyl)glycine,N-(2-hydroxypropyl)-N-(p-tolyl)glycine,N-(2-hydroxypropyl)-N-(3,5-dimethylphenyl)glycine, andN-(2-hydroxypropyl)-N-(vinylbenzyl)glycine, wherein each member of thesixth group may be acidic, anionic, or a salt of one or more members ofa seventh group consisting of sodium, magnesium, calcium and strontium.20. The dental composite restorative of claim 13, wherein the ether linkis formed from a reaction of functionalized vinylbenzyl glycidyl etherwith members of an eighth group consisting of: N(H)-(p-styryl) glycine,N(H)-(phenyl) glycine, N(H)-(p-tolyl) glycine, N(H)-(3,5-dimethylphenyl)glycine, and as N(H)-(vinylbenzyl) glycine, wherein each member of theeighth group may be anionic or a salt of one or more members of a ninthgroup consisting of sodium, magnesium, calcium and strontium.